Filter devices are extensively used to remove particles and microorganisms or purify proteins from biopharmaceutical products. During filtration, materials from a filter device could be extracted into a product and affect its efficacy and safety. The FDA requires the evaluation of filter extractables for both human and animal drug products.
The filter extractables are complex mixtures consisting primarily of low concentrations of oligomers and additives of diverse physical and chemical properties. Since the concentration of other components of the biopharmaceutical product will be higher, the analytical signal for the filter extractables can be masked, and therefore rendering their presence undetectable. Conventionally, the Model Stream Approach (Stone, T. E.; Goel, V.; Leszczak, J. Pharmaceutical Tech. 1994, 116-130) is used to study the extractables present following the filtration step. During this method, the filter device is subjected to a model solvent that simulates specific chemical effects of a pharmaceutical solution. Under this principle, the model solvents are selected to represent the extremes in environment (high or low pH, high salt concentrations, or organic solvents) to which the filter device may be exposed, but not to be identical to the actual contents of the biopharmaceutical product. A “worst case scenario” can be created under aggressive conditions where the filter extractables content is maximized. Analytical techniques such as liquid chromatography UV detection (LCUV), gas chromatography mass spectrometry (GCMS) and Fourier transform infrared spectrometry (FTIR) are employed to detect the presence of extractables in the model solvent during the testing procedure.